Matteucinol, isolated from Miconia chamissois, induces apoptosis in human glioblastoma lines via the intrinsic pathway and inhibits angiogenesis and tumor growth in vivo

被引:12
|
作者
Silva, Ana Gabriela [1 ]
Silva, Viviane Aline O. [2 ]
Oliveira, Renato J. S. [2 ]
de Rezende, Allisson Rodrigues [3 ]
Russo Chagas, Rafael Cesar [1 ]
Santos Pimenta, Lucia Pinheiro [4 ]
Romao, Wanderson [5 ,6 ]
Santos, Helio Batista [7 ]
Thome, Ralph Gruppi [7 ]
Reis, Rui Manuel [2 ,8 ,9 ]
de Azambuja Ribeiro, Rosy Iara Maciel [1 ]
机构
[1] Univ Fed Sao Joao del Rei, Expt Pathol Lab, 400 Sebastiao Goncalves Coelho Chanadour, BR-35501296 Divinopolis, MG, Brazil
[2] Barretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos, SP, Brazil
[3] Univ Estado Minas Gerais, BR-38302192 Ituiutaba, MG, Brazil
[4] Univ Fed Minas Gerais, Inst Exact Sci, Dept Chem, BR-3127090 Belo Horizonte, MG, Brazil
[5] Univ Fed Espirito Santo, Chem Dept, Petrole & Forens Lab, BR-29075910 Vitoria, ES, Brazil
[6] Fed Inst Educ Sci & Technol Espirito Santo, BR-29106010 Vila Velha, ES, Brazil
[7] Fed Univ Sao Joao del Rei UFSJ, Tissue Proc Lab, 400 Sebastiao Goncalves Coelho, Divinopolis, MG, Brazil
[8] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal
[9] ICVS 3Bs PT Govt Associate Lab, P-4806909 Braga, Portugal
关键词
Central nervous system cancer; Melastomataceae; Chicken chorioallantoic membrane assay; DNA damage; Resonance mass spectrometry; Antitumor; DNA-DAMAGE; CANCER; CELLS; TEMOZOLOMIDE; MECHANISMS; COMBINATION; INDUCTION; MIGRATION; INVASION; EXTRACT;
D O I
10.1007/s10637-019-00878-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gliomas account for nearly 70% of the central nervous system tumors and present a median survival of approximately 12-17 months. Studies have shown that administration of novel natural antineoplastic agents is been highly effective for treating gliomas. This study was conducted to investigate the antitumor potential (in vitro and in vivo) of Miconia chamissois Naudin for treating glioblastomas. We investigated the cytotoxicity of the chloroform partition and its sub-fraction in glioblastoma cell lines (GAMG and U251MG) and one normal cell line of astrocytes. The fraction showed cytotoxicity and was selective for tumor cells. Characterization of this fraction revealed a single compound, Matteucinol, which was first identified in the species M. chamissois. Matteucinol promoted cell death via intrinsic apoptosis in the adult glioblastoma lines. In addition, Matteucinol significantly reduced the migration, invasion, and clonogenicity of the tumor cells. Notably, it also reduced tumor growth and angiogenesis in vivo. Moreover, this agent showed synergistic effects with temozolomide, a chemotherapeutic agent commonly used in clinical practice. Our study demonstrates that Matteucinol from M chamissois is a promising compound for the treatment of glioblastomas and may be used along with the existing chemotherapeutic agents for more effective treatment.
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页码:1044 / 1055
页数:12
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